The median maximal percentage reversal of dabigatran's anticoagulant effect was 100% within 4 hours of IV administration, measured according to thrombin time or ecarin clotting time, Charles Pollack, Jr., MD, of Thomas Jefferson University in Philadelphia, and colleagues reported.

Their full cohort analysis of the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) study was published online in the New England Journal of Medicine and presented during a late-breaking session at the International Society on Thrombosis and Haemostasis meeting in Berlin.

Moreover, it took a median 2.5 hours for idarucizumab to stop uncontrolled bleeding in the two-thirds of cases when bleeding could be visualized directly or imaged at 24 hours. Among those given the non-vitamin K oral anticoagulant (NOAC) reversal agent a median 1.6 hours before an emergency procedure, periprocedural hemostasis was normal in 93.4%, mildly abnormal in 5.1%, and moderately abnormal in 1.5%.

At 90 days, thrombotic events had been reported in 6.3% of patients who got IV idarucizumab for uncontrolled bleeding and 7.4% of those who got it before an urgent procedure. Mortality rates were 18.8% and 18.9%, respectively, by Kaplan-Meier estimates.

The mortality rates reported in RE-VERSE AD were on par with that of the first 67 patients enrolled in the ANNEXA-4 study of andexanet alfa (AndexXa) for the reversal of factor Xa inhibitors in patients with serious bleeding, the authors noted. They added that the 30-day rate of thrombotic events (4.8%) was lower than what was shown for ANNEXA-4's first 67 and 102 patients.

"In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran," Pollack's group concluded. "The safety of idarucizumab observed in this study supports its urgent use even if patients later prove to have had little or no circulating dabigatran."

Serious adverse events were reported within 5 days, nonetheless, and in 23.3% of people. These events included delirium, cardiac arrest, and septic shock, which authors chalked up to reflect a worsening of the index event or a coexisting condition -- not a safety signal with idarucizumab.

The full cohort dataset included 301 patients who had uncontrolled bleeding and 202 about to undergo an urgent procedure, with both groups getting 5 g of IV idarucizumab. The two most common causes of uncontrolled bleeding were gastrointestinal bleeding (45.5%) and intracranial hemorrhage (32.6%).

Both arms combined, the overall study population had a median age of 78 years upon enrollment in 2014-2016; men accounted for 54.5% of the population.

Antithrombotic therapy was restarted within 72 hours among 22.9% and 66.8% of the first and second groups, respectively.

Chief among the multicenter, prospective study's limitations was the lack of a control group. In addition, "although case reports suggest that thrombolysis and thrombectomy can be performed safely after dabigatran reversal with idarucizumab, postmarketing surveillance would be helpful to monitor the effectiveness of idarucizumab for this and other indications and to further assess its safety," according to Pollack and colleagues.

NOAC reversal was successful regardless of age, sex, renal function, or dabigatran concentration. "A single 5-g dose of idarucizumab was sufficient in 98% of the patients, and reversal was maintained for 24 hours in most patients," the authors wrote (about 10% of patients had unbound-dabigatran concentrations rebound in 24 hours to cause recurrent elevations in clotting time).

Rates of 30-day mortality were 13.5% in the uncontrolled bleeding arm and 12.6% in the emergent procedure arm. Breaking down the former, deaths reached 16.4% among patients with intracranial hemorrhage, 11.1% among those with gastrointestinal bleeding, and 12.7% among those with other bleeding.

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